Laxatives (Local)

This monograph includes information on the following:

Note: In August, 1997, the U.S. Food and Drug Administration (FDA) announced a proposal to ban the use of phenolphthalein in non-prescription (over-the-counter) products due to long-term safety concerns. Several United State and Canadian laxative manufacturers reformulated their phenolphthalein-containing products prior to or in response to the proposal. Effective January 29, 1999, the FDA issued a final ruling establishing that phenolphthalein is not generally recognized as safe and effective and is misbranded as an over-the-counter stimulant laxative ingredient {107}

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Note: In the treatment of constipation or in the evacuation of the bowel, or in any other conditions in which a laxative is indicated, the advantage of using certain laxative combinations rather than a single laxative preparation has not been established. In some instances, just as with the selection of a single entity laxative, the improper selection of a laxative combination may turn constipation into a more serious condition. FDA's tentative final monograph for laxative drug products for OTC use has listed specific active laxative ingredients to be included in bulk-forming, bulk-forming and lubricant, bulk-forming and stimulant, lubricant and stimulant, lubricant and saline, saline and stimulant, and stimulant combinations.
Some of the laxative combinations contain other active ingredients that have no laxative properties. For example, atropine has been added for its antispasmodic properties probably as an adjunct to relieve constipation-induced cramping. However, a fixed combination of a laxative with any other medication is generally considered irrational and may be unsafe in some combinations.

Accepted

Constipation (prophylaxis)—Oral bulk-forming, lubricant, and stool softener laxatives are indicated prophylactically in patients who should not strain during defecation, such as those with an episiotomy wound, painful thrombosed hemorrhoids, fissures or perianal abscesses, body wall and diaphragmatic hernias, anorectal stenosis, or postmyocardial infarction .[An oral hyperosmotic laxative (polyethylene glycol 3350) is indicated for the prevention of constipation. {102}]

Constipation (treatment)—Oral laxatives are indicated for the short-term relief of constipation. Oral bulk-forming laxatives, stimulant laxatives, and carbon dioxide–releasing suppositories are indicated to facilitate defecation in geriatric patients with diminished colonic motor response. Oral bulk-forming laxatives and stool softener laxatives are preferred to treat constipation that may occur during pregnancy and postpartum to help re-establish normal bowel function or to avoid straining if hemorrhoids are present. {14}An oral hyperosmotic laxative (polyethylene glycol 3350) is indicated for the treatment of occasional constipation. {101}{102}
—In severe cases of constipation, such as with fecal impaction, mineral oil and stool softener laxatives administered orally or rectally are indicated to soften the impacted feces. To help complete the evacuation of the impacted colon, a rectal stimulant or saline laxative may follow.

Bowel evacuation—Pre- and postpartum: Carbon dioxide–releasing suppositories are indicated to evacuate the colon in preparation for delivery and for a few days after to help re-establish normal bowel function.
—Preoperative and
—Pre-radiography: Oral or rectal stimulant and oral saline laxatives, rectal preparations of glycerin, and carbon dioxide–releasing suppositories are also indicated to evacuate the colon in preparation for rectal and bowel examinations, and elective colon surgery.
—Parasites, intestinal (treatment adjunct): Oral saline laxatives are indicated to accelerate excretion of various parasites including nematodes, after anthelmintic therapy.
—Toxicity, nonspecific (treatment adjunct): Oral saline laxatives are also indicated to hasten excretion of poisonous substances (except acids or alkalies) from the gastrointestinal tract.

Hyperammonemia (prophylaxis and treatment)—Lactulose is indicated for the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma.

Biliary tract disorders (treatment)—Dehydrocholic acid is indicated as an adjunct in conditions involving the biliary tract.

Diarrhea (treatment)—Polycarbophil is indicated in the treatment of diarrhea associated with irritable bowel syndrome and diverticulosis, and acute nonspecific diarrhea. [Psyllium hydrophilic mucilloid is used in the treatment of choleretic diarrhea and diarrhea caused by vagotomy, small bowel resection, or disease of the terminal ileum.]

Polyethylene glycol: Prevents absorption by the intestinal tract of the portion of water ingested, serving to hydrate and soften the stool, and promote peristalsis. {101}{102}

Saline: Produces osmotic effect primarily in small intestine by drawing water into the intestinal lumen. Fluid accumulation produces distention, which in turn promotes increased peristalsis and bowel evacuation. During the use of saline laxatives, the release of cholecystokinin from the intestinal mucosa may enhance the laxative effect.

Lubricant:

Increase water retention in the stool by coating surfaces of stool and intestines with a water-immiscible film. Lubricant effect eases passage of contents through intestines. Emulsification of lubricant tends to enhance its ability to soften stool mass.

Stool softener:

Reduce surface film tension of interfacing liquid contents of the bowel, promoting permeation of additional liquid into the stool to form a softer mass.

Stimulant:

Precise mechanism of action is unknown. Thought to increase peristalsis by a direct effect on the smooth intestinal musculature by stimulation of intramural nerve plexi. Also have been shown to promote fluid and ion accumulation in the colon (castor oil acts on the small intestine) to increase the laxative effect.

Antihyperammonemic:

Lactulose decreases blood ammonia concentrations probably as a result of its bacterial degradation, in the colon, into low molecular weight organic acids that decrease the pH of the colonic contents. Acidification of colonic contents results in the retention of ammonia in the colon as the ammonium ion. The osmotic laxative action of the metabolites of lactulose expels the trapped ammonium from the colon.

Hydrocholeretic:

Dehydrocholic acid has no effect on the production of bile salts; however, it increases bile volume and flow by increasing water output, thus producing bile of relatively low specific gravity, viscosity, and total solid content.

Antidiarrheal:

Psyllium hydrophilic mucilloid and polycarbophil"s water and bile salt binding capacity may result in fewer and bulkier stools.

Antihyperlipidemic:

Psyllium hydrophilic mucilloid has an antihyperlipidemic effect. It decreases serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and the ratio of LDL cholesterol to high-density lipoprotein (HDL) cholesterol. Although exact mechanism of psyllium"s antihyperlipidemic effect is not known, it is believed that psyllium increases bile acid secretion, thus draining cholesterol products from the body.

Note: Knowledge of many specifics of the mechanisms of action is limited. The determination of influence of factors such as cyclic-AMP, electrolyte transportation, hormones, and enzymes may change such currently accepted mechanisms.

Precautions to ConsiderCarcinogenicity/Tumorigenicity

Chronic administration of high doses of danthron to mice and rats has resulted in the development of intestinal and liver tumors. Danthron toxicity in humans has not been demonstrated; however, in the U.S., because of the potential risk to humans, the FDA has banned all manufacturing, relabeling, repackaging, and further distribution of human drug products containing danthron.Pregnancy/Reproduction

• Polyethylene glycol 3350: Studies have not been done in humans. Studies have not been done in animals. FDA Pregnancy Category C.

Lubricant—Repeated oral use of mineral oil may decrease absorption of foods, fat-soluble vitamins, and some oral medications. Hypoprothrombinemia and hemorrhagic disease of the neonate have occurred following chronic use during pregnancy.

Stimulant—Castor oil is contraindicated since its use often results in pelvic area engorgement, which may initiate reflex stimulation of the gravid uterus.Breast-feeding

Stimulant—Cascara sagrada and danthron preparations may be distributed into breast milk. The amounts are reportedly large enough to produce loose stools in the infant, although this still remains controversial. {12}Pediatrics

For all laxatives:

Laxatives should not be given to young children (up to 6 years of age) unless prescribed by a physician. Since children are not usually able to describe their symptoms precisely, proper diagnosis should precede the use of a laxative. This will avoid the complication of an existing condition (e.g., appendicitis) or the appearance of more severe side effects.

For lubricant:

Oral mineral oil is not recommended for children up to 6 years of age since patients in this age group are more prone to aspiration of oil droplets, which may produce lipid pneumonia.

For stimulant:

Bisacodyl enteric-coated tablets are not recommended for children up to 6 years of age since patients in this age group may have difficulty swallowing the tablet without chewing it. Gastric irritation may occur if the enteric coating is destroyed by chewing.

For rectal solutions:

Weakness, excessive perspiration, shock, seizures, and/or coma may occur in children with the use of rectal solutions due to water intoxication or dilutional hyponatremia.

Seizures with hypocalcemia may occur as a result of absorption of large amounts of phosphate in children receiving sodium phosphates rectal solution.

Geriatrics

For lubricant:

Oral mineral oil is not recommended for bedridden elderly patients since they are more prone to aspiration of oil droplets, which may produce lipid pneumonia.

For osmotic:

Polyethylene glycol 3350: There is no evidence for special considerations when polyethylene glycol 3350 is administered to elderly patients. However, a higher incidence of diarrhea occurred in elderly nursing home patients when given the recommended dose of 17 grams. Polyethylene glycol 3350 should be discontinued if diarrhea occurs.{101}

For stimulant:

Weakness, incoordination, and orthostatic hypotension may be exacerbated in elderly patients as a result of significant electrolyte loss when stimulant laxatives are used repeatedly to evacuate the colon.

For rectal solutions:

Weakness, excessive perspiration, shock, seizures, and/or coma may occur in elderly patients with the use of rectal solutions due to water intoxication or dilutional hyponatremia.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

For all classes
Diuretics, potassium-sparing, or
Potassium supplements (chronic use or overuse of laxatives may reduce serum potassium concentrations by promoting excessive potassium loss from the intestinal tract; may interfere with potassium-retaining effects of potassium-sparing diuretics)

For bulk-forming
Anticoagulants, oral or
Digitalis glycosides or
Salicylates (concurrent use with cellulose bulk-forming laxatives may reduce the desired effect because of physical binding or other absorptive hindrance; a 2-hour interval between dosage with such medication and laxative dosage is recommended )

» Tetracyclines, oral (concurrent use with calcium polycarbophil may decrease absorption because of possible formation of nonabsorbable complexes with free calcium released after ingestion; patients should be advised not to take calcium polycarbophil laxative within 1 to 2 hours of tetracyclines)

For hyperosmotic-saline, magnesium-containing» Anticoagulants, coumarin- or indandione-derivative, oral or» Digitalis glycosides or
Phenothiazines, especially chlorpromazine (these medications have been shown to have reduced effectiveness in the presence of aluminum- and magnesium-containing antacids; pending further studies, their concurrent administration with magnesium-containing saline hyperosmotic laxatives is best avoided)

» Ciprofloxacin (magnesium-containing laxatives may reduce absorption by chelation of ciprofloxacin, resulting in lower serum and urine concentrations of the antibiotic; therefore, concurrent use is not recommended {13})

» Etidronate (concurrent use may prevent absorption of oral etidronate; patients should be advised to avoid using magnesium-containing laxatives within 2 hours of etidronate {16})

» Sodium polystyrene sulfonate (sodium polystyrene sulfonate may bind with magnesium, preventing neutralization of bicarbonate ions and leading to systemic alkalosis, which may be severe; concurrent use is not recommended, although the risk may be less with rectal administration of the resin)

» Tetracyclines, oral (concurrent use with magnesium-containing laxatives may result in formation of nonabsorbable complexes; patients should be advised not to take these laxatives within 1 to 2 hours of tetracyclines)

For lubricant
Anticoagulants, coumarin- or indandione-derivative, oral or
Contraceptives, oral or
Digitalis glycosides or
Vitamins, fat-soluble, such as A, D, E, and K (concurrent use with mineral oil may interfere with the proper absorption of these or other medications and reduce their effectiveness)

(in addition to interfering with absorption of oral anticoagulants, mineral oil also decreases absorption of vitamin K, which may lead to increased anticoagulant effects)

Stool softener laxatives (concurrent use may cause increased absorption of mineral oil and result in the formation of tumor-like deposits in tissues)

For stimulant
Antacids or
Histamine H 2-receptor antagonists, such as:
Cimetidine
Famotidine
Nizatidine
Ranitidine or
Milk (administration within one hour of bisacodyl tablets may cause the enteric coating to dissolve too rapidly, resulting in gastric or duodenal irritation )

For stool softener
Danthron or
Mineral oil (concurrent use with a stool softener laxative may enhance the systemic absorption of these agents. Although such combinations are intentionally used in some “fixed-dose” laxative preparations, the propensity for toxic effects is greatly increased. Liver injury has been reported with the danthron combination following repeated dosage)

Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results

For stimulant:
Phenolsulfonphthalein (PSP) test (cascara, danthron, and senna may color urine pink to red, red to violet, or red to brown, in event of alkalinity and also may increase the rate of excretion of PSP)

With physiology/laboratory test values

For all classes
Blood glucose concentrations (may be elevated, usually after extended use)

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

Except under special circumstances, this medication should not be used when the following medical problems exist:

For all classes:» Appendicitis, or symptoms of» Bleeding, rectal, undiagnosed» Congestive heart failure or» HypertensionNote: Applies to those preparations containing sodium; an alternative sodium-free laxative may usually be used. Preparations containing less than 5 mg of sodium per dose unit are utilized in many cases.

For hyperosmotic—saline:» Dehydration (may be aggravated by repeated use of saline laxatives)

» Renal function impairment (hyperkalemia and hypermagnesemia may result, especially with preparations containing magnesium and potassium salts; tetany with hypocalcemia and hyperphosphatemia may occur with the use of phosphate salts)

For lubricant:» Dysphagia (oral mineral oil may be aspirated and cause lipid pneumonitis)

» Caution is also recommended with bedridden patients, who may develop lipid pneumonia from aspiration of mineral oil.

Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:Those indicating need for medical attentionIncidence less frequentFor rectal solutions— more frequent with sodium phosphatesRectal irritation (rectal bleeding, blistering, burning, itching, or pain)

Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Laxatives (Oral) and Laxatives (Rectal) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):Before using this medication
Importance of diet, fluids, and exercise» Conditions affecting use, especially:Sensitivity to a particular class of laxative

Pregnancy—

• For saline: May promote sodium retention resulting in edema

• For lubricant: Mineral oil may decrease absorption of foods, fat-soluble vitamins, and medications; possibility of hypoprothrombinemia and hemorrhage in neonate

Results usually obtained in 1 to 2 days after first dose; may require 3 to 5 days

Rectal dosage forms only
Results usually obtained in 2 to 15 minutesPrecautions while using this medication

For all classes» Not using laxatives: —if symptoms of appendicitis are present
—more often than recommended
—unnecessarily (for example, for cold, as tonic, to clean system)
—because bowel movement is missed 1 or 2 days

For bulk-forming
Bulk-forming laxatives are suitable for long-term therapy, if necessary.

For polycarbophil when used as antidiarrheal:
Polycarbophil is available as chewable tablets that absorb up to 60 times their weight in water. They are sometimes utilized to control diarrheal conditions by administering less fluid with each dose.

The usual oral adult dose of calcium polycarbophil when used as antidiarrheal is 1 gram one to four times a day.

The usual oral pediatric dose for children 3 to 6 years of age is 500 mg two times a day; for children 6 to 12 years of age the dose may be given three times a day, but not to exceed 3 grams a day.

For psyllium hydrophilic mucilloid when used as antihyperlipidemic:
Reduced values for serum total cholesterol, low density lipoprotein (LDL), and for the ratio of LDL cholesterol to high density lipoprotein (HDL) cholesterol have been achieved with three 3.4-gram doses of psyllium per day. {08}

For hyperosmotic—lactulose polyethylene glycol, and saline

For lactulose:
Has no effect on small intestine; lowers pH of colon.

Use with caution in diabetics—Contains up to 1.2 grams of lactose and up to 2.2 grams of galactose per 15 mL.

Dose may be mixed with milk or fruit juice to improve flavor.

For lactulose when used as an antihyperammonemic:
The usual oral adult dose of lactulose when used as antihyperammonemic is 20 to 30 grams (30 to 45 mL) three or four times a day. This dose may be adjusted every day or two to produce two to three soft stools daily. In the initial phase of therapy 20 to 30 grams (30 to 45 mL) may be given every hour to induce rapid laxation.

Concurrent use of other laxatives during initial phase of therapy for portal-systemic encephalopathy may result in loose stools and falsely suggest adequate lactulose dosage has been obtained.

For polyethylene glycol 3350:
Has no effect on active absorption or secretion of glucose or electrolytes.

For saline:
Solid forms must be completely dissolved before swallowing.

Because of relatively short response time, saline laxatives are not usually given at bedtime or late in the day unless the dose is relatively small and given with food.

This type of laxative may contain large amounts of sodium (up to 1 gram or more per dose in some preparations).

For lubricant
Commonly administered at bedtime, when slower peristalsis allows longer transit time to improve laxative effect. If administered at bedtime, patient should not be reclining to avoid aspiration of oil droplets.

Because mineral oil may interfere with absorption of oil-soluble nutrients and/or medications, this type of laxative is not administered within 2 hours of meals or other medications.

To avoid oil leakage through the anal sphincter, the dose of mineral oil may be reduced or divided, or a stable emulsion may be used instead.

For stimulant
Many preparations of this group are administered at bedtime with a snack to produce results in the morning— except castor oil. Because of its shorter response time, castor oil is not usually taken at bedtime or late in the day.

Bisacodyl tannex (bisacodyl and tannic acid complex) should not be used if multiple enemas are required. If absorbed in sufficient amounts, tannic acid is hepatotoxic.

For dehydrocholic acid when used as hydrocholeretic:
The usual oral adult dose of dehydrocholic acid when used as hydrocholeretic is 244 to 500 mg three times a day after meals.

For stool softeners
Because stool softener laxatives may increase absorption of other laxatives, including mineral oil, they are not given within 2 hours of such preparations. Patients should be informed.

The bitter taste of some liquid preparations of this type of laxative may be improved by diluting each dose in milk or fruit juice.

For oral dosage forms
With the possible exception of bulk-forming laxatives, more rapid results are obtained when laxatives are taken on an empty stomach. When taken with food and/or at bedtime, results tend to be delayed.

Intake of at least 6 to 8 full glasses (240 mL each) of fluid per day is necessary to aid in producing a soft stool and to protect the patient against dehydration when large volumes of water are lost with passage of the stool.

For rectal dosage forms
Lubrication of anus with petroleum jelly is recommended to prevent rectal abrasion and/or laceration produced by the insertion of a hard enema tip.

Lubrication of suppositories with mineral oil or petrolatum is not recommended since it may interfere with the action of the suppository. Instead, the suppository should be moistened with water by placing under a water tap for 30 seconds or in a cup of water for at least 10 seconds, before rectal insertion.

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